title: Identification of a novel BRCA2 and CHEK2 A-C-G-C haplotype in Turkish patients affected with breast cancer.
abstract: BACKGROUND
  Many breast cancers are caused by certain rare and familial mutations in the high or moderate penetrance genes BRCA1, BRCA2 and CHEK2. The aim of this study was to examine the allele and genotype frequencies of seven mutations in BRCA1, BRCA2 and CHEK2 genes in breast cancer patients and to investigate their isolated and combined associations with breast cancer risk.
  
  
  METHODS
  We genotyped seven mutations in BRCA1, BRCA2 and CHEK2 genes and then analyzed single variations and haplotype associations in 106 breast cancer patients and 80 healthy controls.
  
  
  RESULTS
  We found significant associations in the analyses of CHEK2- 1100delC (p=0.001) and BRCA1-5382insC (p=0.021) mutations in breast cancer patients compared to controls. The highest risk was observed among breast cancer patients carrying both CHEK2-1100delC and BRCA2- Met784Val mutations (OR=0.093; 95%CI 0.021-0.423; p=0.001). We identified one previously undescribed BRCA2 and a CHEK2 four-marker haplotype of A-C-G-C which was overrepresented (?2=7.655; p=0.0057) in the patient group compared to controls.
  
  
  CONCLUSIONS
  In this study, we identified a previously undescribed BRCA2 and CHEK2 A-C-G-C haplotype in association with the breast cancer in our population. Our results further suggest that the CHEK2-1100delC mutation in combination with BRCA2-Met784Val may lead to an unexpected high risk which needs to be confirmed in larger cohorts in order to better understand their role in the development and prognosis of breast cancer.
authors.affiliation: Department of Neuroscience, Institute for Experimental Medicine Research, Istanbul University, Istanbul, Turkey.
authors.forename: Hazal
authors.initials: H
authors.lastname: Haytural
authors.forename: Nazli
authors.initials: N
authors.lastname: Yalcinkaya
authors.forename: Gokce
authors.initials: G
authors.lastname: Akan
authors.forename: Soykan
authors.initials: S
authors.lastname: Arikan
authors.forename: Elif
authors.initials: E
authors.lastname: Ozkok
authors.forename: Bedia
authors.initials: B
authors.lastname: Cakmakoglu
authors.forename: Ilhan
authors.initials: I
authors.lastname: Yaylim
authors.forename: Makbule
authors.initials: M
authors.lastname: Aydin
authors.forename: Fatmahan
authors.initials: F
authors.lastname: Atalar
mesh_terms: D000328:Adult; D000368:Aged; D024682:BRCA2 Protein / Q000235:genetics*; D014408:Biomarkers, Tumor / Q000235:genetics*; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology; D016022:Case-Control Studies; D064447:Checkpoint Kinase 2 / Q000235:genetics*; D005260:Female; D005500:Follow-Up Studies; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006239:Haplotypes / Q000235:genetics*; D006801:Humans; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D009367:Neoplasm Staging; D011379:Prognosis; D012307:Risk Factors; D014421:Turkey
chemical_list: D024682:BRCA2 Protein; C551750:BRCA2 protein, human; D014408:Biomarkers, Tumor; D064447:Checkpoint Kinase 2; C578634:CHEK2 protein, human